Optimization of a synthetic siRNA delivery for the treatment of rhabdomyosarcoma

Lesko, Ewa; Miękus, Katarzyna; Grabowska, Agnieszka; Gładyś, Aleksandra; Majka, Marcin

doi:10.2478/s11535-008-0042-5

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…In the present study, thiolated and nonthiolated TMC (Figure 1) were investigated for siRNA delivery and gene silencing. The silencing activity and the cellular toxicity of polyplexes based on these biodegradable polymers were compared with those based on the regularly used lipidic transfection agent Lipofectamine (35).…”

Section: Introductionmentioning

confidence: 99%

Gene Silencing Activity of siRNA Polyplexes Based on Thiolated N,N,N-Trimethylated Chitosan

et al. 2010

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N,N,N-Trimethylated chitosan (TMC) is a biodegradable polymer emerging as a promising nonviral vector for nucleic acid and protein delivery. In the present study, we investigated whether the introduction of thiol groups in TMC enhances the extracellular stability of the complexes based on this polymer and promotes the intracellular release of siRNA. The gene silencing activity and the cellular cytotoxicity of polyplexes based on thiolated TMC were compared with those based on the nonthiolated counterpart and the regularly used lipidic transfection agent Lipofectamine. Incubation of H1299 human lung cancer cells expressing firefly luciferase with siRNA/thiolated TMC polyplexes resulted in 60-80% gene silencing activity, whereas complexes based on nonthiolated TMC showed less silencing (40%). The silencing activity of the complexes based on Lipofectamine 2000 was about 60-70%. Importantly, the TMC-SH polyplexes retained their silencing activity in the presence of hyaluronic acid, while nonthiolated TMC polyplexes hardly showed any silencing activity, demonstrating their stability against competing anionic macromolecules. Under the experimental conditions tested, the cytotoxicity of the thiolated and nonthiolated siRNA complexes was lower than those based on Lipofectamine. Given the good extracellular stability and good silencing activity, it is concluded that polyplexes based on TMC-SH are attractive systems for further in vivo evaluations.

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Section: Introductionmentioning

confidence: 99%

Gene Silencing Activity of siRNA Polyplexes Based on Thiolated N,N,N-Trimethylated Chitosan

et al. 2010

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“…Similarly, lncRNAs that are found in body fluids have demonstrated a utility to be used as fluidbased non-invasive markers for clinical use. Therapeutic benefit can be obtained through RNA-based therapeutic strategies, such as siRNA and microRNA, or using small molecule compounds designed specifically to interact with target lncRNAs or ribonucleoprotein complexes [47]. It is tempting to speculate that a multitude of lncRNAs may interrupt specific steps in numerous tumor suppressive and oncogenic pathways.…”

Section: Resultsmentioning

confidence: 99%

Roles of long noncoding RNAs in Hepatocellular Carcinoma

2016

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Long noncoding RNAs (lncRNAs) are nonprotein coding transcripts longer than 200 nucleotides. Aberrant expression of lncRNAs has been found to be associated with hepatocellular carcinoma, one of the most malignant tumors. In this paper, we give a systematic and comprehensive review of existing literature about the involvement of lncRNAs in hepatocellular carcinoma. To date, evidence suggests that a number of lncRNAs, including HEIH, H19, HOTAIR, MALAT1, and PVT1, may regulate the transcription of target genes by recruiting histone-modifying complexes. Under certain circumstances, lncRNAs form RNA-dsDNA triplexes. Certain lncRNAs, such as HULC, HOTAIR, H19, HOTTIP and PTENP1, exhibit their biological roles by associating with microRNAs (miRNAs). In addition, by complementary base pairing with mRNAs or forming complexes with RNA binding proteins (RBPs), lncRNA-ATB, MALAT1 and PCNA-AS1 may mediate mRNA stability and splicing. In conclusion, interactions with DNA, RNA and proteins appears to be involved in lncRNAs' participation in tumorigenesis and developmental processes related to hepatocellular carcinoma.

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